Towards Clinical Innovation with Extracellular Vesicles

<p>Extracellular vesicles (EVs), known as exosomes and microvesicles, serve as versatile intercellular communication vehicles. Cell-to-cell communication via EV cargo contributes to cancer progression in the tumor microenvironment and pre-metastatic niche. Therefore, EVs and their components represent a novel class of therapeutic targets. For example, we focused on the screening of small-molecule inhibitors for EV secretion in ovarian cancer cells. We used an original screening system based on ExoScreen assay for monitoring CD9 positive EV secretion. Using this screening system and a chemical compound library containing 1271 small molecules, inhibitors for EV secretion were identified in the ovarian cancer cell line ES-2. We are now analyzing the effects of these candidate molecules on gene expression in cancer cells. Furthermore, the circulating EVs have also been of interest as a source for liquid biopsies. EVs in body fluids provide a reliable source of proteins and miRNAs for cancer biomarkers. Recently we identified novel pancreatic cancer biomarkers, EV-associated GPRC5C and EPS8, using our improved EV-associated protein purification method and proteomic analysis. Finally, we showed that GPRC5C- or EPS8-positive EVs were biomarkers that have the potential to detect stage I early pancreatic cancer and small recurrent tumors detected by computed tomography. Emerging our data suggest that EVs play an important role in cancer pathogenesis and may potentially be therapeutics and biomarkers.</p>